Bovine leukemia virus (BLV) is a retrovirus infection of dairy and beef cattle that causes malignant lymphoma. The clinical signs of BLV infection become evident as the tumors invade different tissues. Symptoms associated with BLV may include weight loss, decreased milk production, enlarged lymph nodes, loss of appetite, rear-limb weakness or paralysis, fever, protruding eyeballs, gastrointestinal obstruction, abnormal heartbeat, and abnormal blood lymphocyte count. Bovine malignant lymphoma (BML) may cause significant morbidity and mortality in some infected herds, especially when the prevalence of infection is high. BML usually is fatal because there are no drugs to treat this type of cancer.
Significant economic losses in domestic and international dairy and beef cattle herds occur each year as a consequence of BML. Additional economic losses resulting from BLV infection come from trade restrictions on infected animals and their germplasm.
In 1996 the National Animal Health Monitoring System (NAHMS), conducted by the U.S. Department of Agriculture-Animal and Plant Health Inspection Service-Veterinary Services (USDA-APHIS-VS), conducted an assessment of BLV prevalence in U.S. dairy herds. Between February and May of 1996, federal and state animal health officials contacted randomly selected dairy operations with at least 30 milk cows in 20 states, representing about 79 percent of the U.S. dairy cow population. Blood samples were collected from milk cows on 1007 participating operations and sent to the National Veterinary Services Laboratories for BLV testing using the agar gel immunodiffusion (AGID) test.
Results from this study indicated that 89 percent of all U.S. dairy operations harbored animals seropositive for BLV, while 43.5 percent of U.S. beef cattle operations harbored animals seropositive for BLV. BLV prevalence in the West, Midwest, and Northeast regions was between 87 to 89 percent. The operation prevalence in the Southeast region was 99 percent. BLV operational prevalence (94.7%) in herds with 200-plus cows was slightly higher than the prevalence in smaller operations. In the Southeast region, the individual-cow prevalence (68.8%) was much higher than in other regions. The individual-cow prevalence in operations with 200-plus cows (47.2%) was higher than the prevalence in smaller herds. The individual-cow prevalence was at least 25 percent on 7,546 of the positive operations.
Higher rates of infection are noted in larger herd units and in warmer climates. Transmission by biting insects is believed to be limited, but other practices in warm climates may amplify BLV (e.g., such as immunization against blood-borne infections like anaplasmosis and piroplasmosis using vaccines of blood origin). BLV infection among European dairy breeds in tropical countries is quite high. These milk-poor nations have even less economic incentive and capacity to attempt eradication of BLV than does the USA.
Parallels between the pathogenesis and epidemiology of BLV and Human T Cell Leukemia Virus 1 (HTLV-1) are beginning to be recognized. For example, the complex oncoviruses (e.g., BLV and HTLV-1) depend upon the function of Rex protein to mediate the export and expression of intron-containing viral RNAs encoding the Gag, Pol, and Env proteins needed for generating infection competent viral particles.
Despite an active retrovirus-specific cellular and humoral immune response, immune competent individuals fail to resolve infection early in the course of BLV, HTLV-1 and HTLV-2, and Human Immunodeficiency Virus (HIV) infections. (See, Piper, C. E., et al., Cancer Res., 35(10):2714-6 [1975]). BLV Virus apparently spreads because the immune response fails to eliminate infected cells, and in HTLV and HIV, a potent immune response does not correlate with slow progressor status (Pollari, F. L., et al., Can. J. Vet. Res., 56(4):289-95 [1992]). Activation and proliferation of cells, even immune cells, is required for proviral integration and retroviral replication. Thus, it appears that the mechanism responsible for the spread of BLV centers on immune responses that would activate infected B cells and prompt viral replication. When a BLV-infected animal responds to any antigen, bystander, provirus-carrying B cells at the site will be activated, triggering further BLV replication cycles and increasing the numbers of cells carrying integrated provirus. Thus, approaches to control BLV by enhancing the animal's immune response to the BLV virus are unlikely to succeed.
What is needed are compositions and methods for controlling the spread of BLV that are not based on conventional vaccinal or pharmacologic means.